DESCRIPTION: (adapted verbatim from the investigator's abstract) Patients with Ewing's sarcoma family of tumors who are at high-risk for relapse are those with metastic disease at diagnosis, with a primary tumor of the humerus, femur or trunk, or with localized but bulky (>8cm) disease at the time of diagnosis. At 2 y>60% will have recurrence in lung, bone or bone marrow. Recently, a very high-dose short-term VAC regimen was shown to have excellent anti-tumor activity and manageable toxicity in this high-risk group of patients. The randomized phase II trial described in this proposal builds on this dose-intensive regimen by adding the cardioprotectant Dexrazoxane (dxr) and increasing the dose of A from 75mg/m(2) to 90m/m(2) per course. In addition ImmTher, a new immune modulator that activates monocyte-mediated tumor cell killing will be given to 2/3 of the patients following completion of all primary chemotherapy, surgery and/or radiotherapy. ImmTher is a lipophilic disaccharide dipeptide derivative of muramyl dipeptide encapsulated into liposomes. When given i.v. ImmTher induced regression of lung and liver metastases in a Phase I study. Since the lung is a common site of metastasis in Ewing's Sarcoma, our goal is to activate pulmonary macrophages to destroy residual tumor cells. Patients will be stratified according to the presence of bony metastases and then randomized at study entry in a 2:1 ratio in favor of receiving ImmTher. ImmTher will be given weekly for 52 weeks. This 2:1 randomization strategy was requested by the FDA during the initial protocol development phase so that more information on the toxicity of long-term ImmTher administration could be obtained. The specific aims of this phase II trial are: (I) determine whether ImmTher given following dose-intensive VAC can improve the 2-yr disease-free survival and 3-yr long term survival in this high-risk group. (II) Evaluate the immunomodulatory activity of ImmTher in patients following dose- intensive chemotherapy. Plasma TNGa, IL-6, IL-8, IL1a, IL-1B, neopterin, IL-12, IFNy and peripheral blood monocyte tumoricidal activity will be monitored to this end before, during and after ImmTher treatment. (III) As a pilot study we will also monitor serum VEGF levels in all patients throughout the treatment period and during follow-up visits. Our hypothesis is that VEGF may contribute to the growth and invasion of Ewing's sarcoma and that serum VEGF levels may predict relapse.